The goals of this proposal are to understand at the metabolic and molecular level the pathogeneses of several specific inherited disorders of purine and pyrimidine metabolism. We are particularly interested in increasing further the resolution of our understanding of the pathogenesis of the immunologic disorders in humans associated with the inherited deficiency of purine nucleoside phosphorylase and of adenosine deaminase. Goals which we set for the current year include (1.) the delineation of the specific nucleoside kinases responsible for the phosphorylation of the potentially toxic deoxynucleoside substrates which accumulate in humans deficient in adenosine or purine nucleoside phosphorylase (2.) the further characterization of the molecular nature of the ribonucleotide reductase from mammalian cells and the role of that key enzyme in immunodeficiency diseases and mutagenesis.